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1.
Front Neurosci ; 17: 1196722, 2023.
Article in English | MEDLINE | ID: mdl-37284659

ABSTRACT

Objective: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder affecting the upper and lower motor neurons. Though the pathogenesis of ALS is still unclear, exploring the associations between risk factors and ALS can provide reliable evidence to find the pathogenesis. This meta-analysis aims to synthesize all related risk factors of ALS to understand this disease comprehensively. Methods: We searched the following databases: PubMed, EMBASE, Cochrane library, Web of Science, and Scopus. Moreover, observational studies, including cohort studies, and case-control studies, were included in this meta-analysis. Results: A total of 36 eligible observational studies were included, and 10 of them were cohort studies and the rest were case-control studies. We found six factors exacerbated the progression of disease: head trauma (OR = 1.26, 95% CI = 1.13, 1.40), physical activity (OR = 1.06, 95% CI = 1.04, 1.09), electric shock (OR = 2.72, 95% CI = 1.62, 4.56), military service (OR = 1.34, 95% CI = 1.11, 1.61), pesticides (OR = 1.96, 95% CI = 1.7, 2.26), and lead exposure (OR = 2.31, 95% CI = 1.44, 3.71). Of note, type 2 diabetes mellitus was a protective factor for ALS. However, cerebrovascular disease (OR = 0.99, 95% CI = 0.75, 1.29), agriculture (OR = 1.22, 95% CI = 0.74, 1.99), industry (OR = 1.24, 95% CI = 0.81, 1.91), service (OR = 0.47, 95% CI = 0.19, 1.17), smoking (OR = 1.25, 95% CI = 0.5, 3.09), chemicals (OR = 2.45, 95% CI = 0.89, 6.77), and heavy metal (OR = 1.5, 95% CI = 0.47, 4.84) were not risk factors for ALS based on meta-analyses. Conclusions: Head trauma, physical activity, electric shock, military service, pesticides, and lead were risk factors for ALS onset and progression. But DM was a protective factor. This finding provides a better understanding of ALS risk factors with strong evidence for clinicians to rationalize clinical intervention strategies. INPLSY registration number: https://inplasy.com/inplasy-2022-9-0118/, INPLASY202290118.

2.
J Neurol ; 270(10): 4729-4743, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37369861

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the upper and lower motor neurons, which can lead to death from respiratory failure within 3-5 years after the onset of this disease. Nowadays, no drug can effectively slow down the progression of this disease. High-calorie therapy, an emerging complementary alternative treatment, has been reported in studies to prolong the survival time of patients, prevent muscle atrophy and provide a better prognosis. However, no systematic review and meta-analysis were performed to summarize the evidence of this therapy. This meta-analysis comprehensively evaluates the effectiveness and safety of high-calorie therapy for treating ALS. METHODS: We searched the electronic databases from inception to 1 April 2023: PubMed, Embase, Web of Science, Cochrane Library, Scopus, Ovid/Medline, and ProQuest. Randomized controlled trials (RCTs) that met the inclusion criteria were performed by meta-analysis. All statistical analyses were performed in STATA software. RESULTS: A total of six eligible RCTs were included in this meta-analysis, involving 370 ALS patients. The meta-analyses showed that high-calorie therapy had superiority in improving body weight (SMD = 1, 95% CI 0.36, 1.65) and BMI (SMD = 0.83, 95% CI 0.02, 1.63). With respect to safety, there was no difference between the high-calorie therapy and the control group regarding the number of adverse events (RR = 3.61, 95% CI 0.08, 162.49). However, ALSFRS-R scores (SMD = 0.34, 95% CI - 0.4, 1.08), survival rate (RR = 1.23, 95% CI 0.98, 1.55), and lipid profile (LDL: SMD = 0.21, 95% CI - 0.33, 0.75; HDL: SMD = 0.17, 95% CI - 0.37, 0.71; TC: SMD = 0.21, 95% CI - 0.33, 0.75), CRP (SMD = 0.85, 95% CI - 1.37, 3.06) showed no significant difference compared to the control groups. CONCLUSIONS: High-calorie therapy is effective in gaining weight and BMI with few side effects. However, no significant superiority was detected in ALSFRS-R scores, survival time, lipid profile, and CRP indicator. The overall quality of the included studies is high, and the results have some credibility, but future corroboration by high-quality RCTs is also expected.


Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Amyotrophic Lateral Sclerosis/drug therapy , Lipids/therapeutic use
3.
Medicine (Baltimore) ; 101(7): e28893, 2022 Feb 18.
Article in English | MEDLINE | ID: mdl-35363208

ABSTRACT

BACKGROUND: Stress urinary incontinence (SUI) is one of the common diseases in female urinary system diseases, and the incidence is increasing year by year. Moxibustion therapy, as a kind of acupuncture therapy, has been widely used in the clinical treatment of SUI, but its therapeutic effect and safety have not been scientifically and systematically evaluated. Therefore, the protocol of this systematic review we propose this time is to scientifically evaluate the effectiveness and safety of moxibustion in the treatment of female stress urinary incontinence (FSUI). METHODS: The following 8 electronic databases will be searched from establishment to December 2021: PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database, Wanfang Database, China Biology Medicine disc. All randomized controlled trials of moxibustion in the treatment of FSUI will be searched in the above electronic databases. Two reviewers will independently complete research selection, data extraction, and research quality evaluation. After screening the studies, the quality of the included studies will be evaluated according to the quality standards specified in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). The primary outcome of included studies is the change from baseline in urine leakage measured by the 1-hour pad test. Secondary outcomes include: the short-form of the International Consultation on Incontinence Questionnaire, the mean 72-hour urinary incontinence episode frequency, self-assessment of the patient's treatment effect, severity of urinary incontinence, and adverse events. Two reviewers will independently conduct study selection, data extraction, risk of bias assessment, and study quality assessment. And the STATA 14.0 software will be implemented for data synthesis and meta-analysis. RESULTS: The result of this meta-analysis will be submitted to peer-reviewed journals for publication, and a comprehensive review of current evidence will be conducted. CONCLUSIONS: The conclusion of this systematic review will provide evidence for judging whether moxibustion is a safer and more effective intervention for female stress urinary incontinence. TRIAL REGISTRATION NUMBER: The protocol has been registered on INPLASY2021120052.


Subject(s)
Moxibustion , Urinary Incontinence, Stress , Female , Humans , Meta-Analysis as Topic , Moxibustion/adverse effects , Moxibustion/methods , Research Design , Systematic Reviews as Topic , Urinary Incontinence, Stress/etiology , Urinary Incontinence, Stress/therapy
4.
Medicine (Baltimore) ; 100(1): e24121, 2021 Jan 08.
Article in English | MEDLINE | ID: mdl-33429784

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic disease of the nasal mucosa globally. Several clinical studies have shown that sanfu acupoint herbal patching (SAHP) has obvious advantages in treating AR. Therefore, the purpose of this systematic review is to evaluate the effectiveness and safety of SAHP for treating AR. METHOD: The following 9 electronic databases will be searched from January 2010 to October 2020: PubMed/Medline, Web of Science, Cochrane Library, EMBASE, China National Knowledge Infrastructure, VIP Database, WANFANG Database, China Biology Medicine disc. The selection of the studies and the extraction of the data are independently completed by 2 reviewers. The qualities of the studies are evaluated by Cochrane risk-of-bias tool. The main outcome of included studies is total effective rate. Secondary outcomes are Total Nasal Symptom Score, recurrence rate, Rhinitis Quality of Life Questionnaire, adverse events and laboratory indicators: serum immunoglobulin E (IgE). And the STATA 14.0 software will be implemented for data synthesis and meta-analysis. RESULTS: The review is ongoing, no results can be reported. CONCLUSIONS: The systematic review will provide a better option for patients to treat AR. REGISTRATION NUMBER: INPLASY2020100101.


Subject(s)
Acupuncture Points , Clinical Protocols , Medicine, Chinese Traditional/standards , Rhinitis, Allergic/therapy , Humans , Meta-Analysis as Topic , Systematic Reviews as Topic
5.
Medicine (Baltimore) ; 99(31): e21544, 2020 Jul 31.
Article in English | MEDLINE | ID: mdl-32756210

ABSTRACT

BACKGROUND: Postoperative nausea and vomiting (PONV) is a main complication of surgery, and by now, drugs cannot prevent it completely. Some meta-analyses have proved acupuncture therapy can prevent PONV. However, it is still controversial whether noninvasive acupuncture therapies are comparable with invasive ones. This study uses Bayesian network meta-analysis to compare the effectiveness of different forms of acupuncture in preventing PONV. METHODS: PubMed/Medline, Cochrane library, Web of Science, Ebsco, Ovid/Embase, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc will be searched from inception to May 2020. All randomized control trails meet the criterion will be included. Quality evaluation of included studies will be implemented with Cochrane risk-of-bias tool. STATA 14.0 will be used to perform pairwise meta-analysis. Addis 1.16.8, R 3.6.3, OpenBUGS 3.2.3, and STATA 14.0 will be used to conduct network meta-analysis. The evidence will be assessed by the grading of recommendations assessment, development, and evaluation approach using GRADE Profiler 3.6. RESULTS: The results of this review will be submitted to a peer-reviewed journal for publication and generate a comprehensive review of current evidence. CONCLUSION: Our results will help to improve the clinical decision-making ability and policy-making in PONV domain. SYSTEMATIC REVIEW REGISTRATION: The protocol has been registered on INPLASY 202060108.


Subject(s)
Acupuncture Therapy/methods , Postoperative Nausea and Vomiting/prevention & control , Acupuncture Therapy/adverse effects , Bayes Theorem , Humans , Network Meta-Analysis , Randomized Controlled Trials as Topic , Research Design , Meta-Analysis as Topic
6.
Anal Bioanal Chem ; 412(24): 6009-6022, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32173790

ABSTRACT

Total internal reflection (TIR) optical spectroscopies have been widely used for decades as non-destructive and surface-sensitive measurements of thin films and interfaces. Under TIR conditions, an evanescent wave propagates into the sample layer within a region approximately 50 nm to 2 µm from the interface, which limits the spatial extent of the optical signal. The most common TIR optical spectroscopies are fluorescence (i.e., TIRF) and infrared spectroscopy (i.e., attenuated total reflection infrared). Despite the first report of TIR Raman spectroscopy appearing in 1973, this method has not received the same attention to date. While TIR Raman methods can provide chemical specific information, it has been outshined in many respects by surface-enhanced Raman spectroscopy (SERS). TIR Raman spectroscopy, however, is garnering more interest for analyzing the chemical and physical properties of thin polymer films, self-assembled monolayers (SAMs), multilayered systems, and adsorption at an interface. Herein, we discuss the early experimental and computational work that laid the foundation for recent developments in the use of TIR Raman techniques. Recent applications of TIR Raman spectroscopy as well as modern TIR Raman instruments capable of measuring monolayer-sensitive vibrational modes on smooth metallic surfaces are also discussed. The use of TIR Raman spectroscopy has been on a rise and will continue to push the limits for chemical specific interfacial and thin film measurements. Graphical abstract Total internal reflection (TIR) Raman spectroscopy can extract the chemical and physical information from thin films and adsorbates.

7.
Anal Chim Acta ; 1048: 123-131, 2019 Feb 07.
Article in English | MEDLINE | ID: mdl-30598142

ABSTRACT

Experimental data for waveguide-coupled surface-plasmon-polariton (SPP) cones generated from dielectric waveguides is presented. The results demonstrate a simpler route to collect plasmon waveguide resonance (i.e., PWR) data. In the reverse-Kretschmann configuration (illumination from the sample side) and Kretschmann configuration (illumination from the prism side), all the waveguide modes are excited simultaneously with p- or s-polarized incident light, which permits rapid acquisition of PWR data without the need to scan the incident angle or wavelength, in the former configuration. The concentric SPP cone properties depend on the thickness and index of refraction of the waveguide. The angular intensity pattern of the cone is well-matched to simulation results in the reverse-Kretschmann configuration, and is found to be dependent on the polarization of the incident light and the polarization of the waveguide mode. In the Kretschmann geometry, all waveguide-coupled SPP cones are measured at incident angles that produce attenuated light reflectivity. In addition, the enhanced electric field produced under total internal reflection allows high signal-to-noise ratio multimodal spectroscopies (e.g., Raman scattering, luminescence) to measure the chemical content of the waveguide film, which traditionally is not measured with PWR.

8.
Biochim Biophys Acta Biomembr ; 1861(1): 43-49, 2019 01.
Article in English | MEDLINE | ID: mdl-30401627

ABSTRACT

The interactions between the cytoplasmic protein diaphanous-1 (Diaph1) and the receptor for advanced glycation endproducts (RAGE) drive the negative consequences of RAGE signaling in several disease processes. Reported in this work is how Diaph1 affects the nanoscale clustering and diffusion of RAGE measured using super-resolution stochastic optical reconstruction microscopy (STORM) and single particle tracking (SPT). Altering the Diaph1 binding site has a different impact on RAGE diffusion compared to when Diaph1 expression is reduced in HEK293 cells. In cells with reduced Diaph1 expression (RAGE-Diaph1-/-), the average RAGE diffusion coefficient is increased by 35%. RAGE diffusion is known to be influenced by the dynamics of the actin cytoskeleton. Actin labeling shows that a reduced Diaph1 expression leads to cells with reduced filopodia density and length. In contrast, when two RAGE amino acids that interact with Diaph1 are mutated (RAGERQ/AA), the average RAGE diffusion coefficient is decreased by 16%. Since RAGE diffusion is slowed when the interaction between Diaph1 and RAGE is disrupted, the interaction of the two proteins results in faster RAGE diffusion. In both RAGERQ/AA and RAGE-Diaph1-/- cells the number and size of RAGE clusters are decreased compared to cells expressing RAGE and native concentrations of Diaph1. This work shows that Diaph1 has a role in affecting RAGE clusters and diffusion.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Actin Cytoskeleton/metabolism , Actins/chemistry , Binding Sites , Cluster Analysis , Diffusion , Formins , HEK293 Cells , Humans , Microscopy , Mutation , Probability , Protein Binding , Pseudopodia/metabolism , Signal Transduction , Stochastic Processes
9.
Eur Biophys J ; 47(1): 39-48, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28623388

ABSTRACT

Membrane diffusion is one of the key mechanisms in the cellular function of receptors. The signaling of receptors for advanced glycation end-products (RAGE) has been extensively studied in the context of several pathological conditions, however, very little is known about RAGE diffusion. To fill this gap, RAGE lateral diffusion is probed in native, cholesterol-depleted, and cytoskeleton-altered cellular conditions. In native GM07373 cellular conditions, RAGE has a 90% mobile fraction and an average diffusion coefficient of 0.3 µm2/s. When depolymerization of the actin cytoskeleton is inhibited with the small molecule jasplakinolide (Jsp), the RAGE mobile fraction and diffusion coefficient decrease by 22 and 37%, respectively. In contrast, depolymerizing the filamentous actin cytoskeleton using the small molecule cytochalasin D (CD) does not alter the RAGE diffusion properties. There is a 70 and 50% decrease in phosphorylation of extracellular signal-regulated kinase (p-ERK) when the actin cytoskeleton is disrupted by CD or Jsp, respectively, in RAGE-expressing GM07373 cells. Disrupting the actin cytoskeleton in GM07373 cells that do not express detectable amounts of RAGE results in no change in p-ERK. Cholesterol depletion results in no statistically significant change in the diffusion properties of RAGE or p-ERK. This work presents a strong link between the actin cytoskeleton and RAGE diffusion and downstream signaling, and serves to further our understanding of the factors influencing RAGE lateral diffusion.


Subject(s)
Receptor for Advanced Glycation End Products/metabolism , Signal Transduction , Actin Cytoskeleton/metabolism , Animals , Cattle , Cell Line , Cell Membrane/metabolism , Chronic Disease , Diffusion , Inflammation/pathology
10.
Biochim Biophys Acta ; 1858(12): 3141-3149, 2016 12.
Article in English | MEDLINE | ID: mdl-27720951

ABSTRACT

The effect of ligand on the lateral diffusion of receptor for advanced glycation endproducts (RAGE), a receptor involved in numerous pathological conditions, remains unknown. Single particle tracking experiments that use quantum dots specifically bound to hemagglutinin (HA)-tagged RAGE (HA-RAGE) are reported to elucidate the effect of ligand binding on HA-RAGE diffusion in GM07373 cell membranes. The ligand used in these studies is methylglyoxal modified-bovine serum albumin (MGO-BSA) containing advanced glycation end products modifications. The binding affinity between soluble RAGE and MGO-BSA increases by 1.8 to 9.7-fold as the percent primary amine modification increases from 24 to 74% and with increasing negative charge on the MGO-BSA. Ligand incubation affects the HA-RAGE diffusion coefficient, the radius of confinement, and duration of confinement. There is, however, no correlation between MGO-BSA ligand binding affinity with soluble RAGE and the extent of the changes in HA-RAGE lateral diffusion. The ligand induced changes to HA-RAGE lateral diffusion do not occur when cholesterol is depleted from the cell membrane, indicating the mechanism for ligand-induced changes to HA-RAGE diffusion is cholesterol dependent. The results presented here serve as a first step in unraveling how ligand influences RAGE lateral diffusion.


Subject(s)
Receptor for Advanced Glycation End Products/metabolism , Animals , Cattle , Cells, Cultured , Diffusion , Extracellular Signal-Regulated MAP Kinases/metabolism , Ligands , Quantum Dots , Receptor for Advanced Glycation End Products/chemistry , Serum Albumin, Bovine/metabolism
11.
ACS Nano ; 9(3): 2948-59, 2015 Mar 24.
Article in English | MEDLINE | ID: mdl-25661423

ABSTRACT

Organometallic halide perovskites CH3NH3PbX3 (X = I, Br, Cl) have quickly become one of the most promising semiconductors for solar cells, with photovoltaics made of these materials reaching power conversion efficiencies of near 20%. Improving our ability to harness the full potential of organometal halide perovskites will require more controllable syntheses that permit a detailed understanding of their fundamental chemistry and photophysics. In this manuscript, we systematically synthesize CH3NH3PbX3 (X = I, Br) nanocrystals with different morphologies (dots, rods, plates or sheets) by using different solvents and capping ligands. CH3NH3PbX3 nanowires and nanorods capped with octylammonium halides show relatively higher photoluminescence (PL) quantum yields and long PL lifetimes. CH3NH3PbI3 nanowires monitored at the single particle level show shape-correlated PL emission across whole particles, with little photobleaching observed and very few off periods. This work highlights the potential of low-dimensional organometal halide perovskite semiconductors in constructing new porous and nanostructured solar cell architectures, as well as in applying these materials to other fields such as light-emitting devices and single particle imaging and tracking.

12.
Bioorg Med Chem Lett ; 25(1): 148-52, 2015 Jan 01.
Article in English | MEDLINE | ID: mdl-25453788

ABSTRACT

A novel conjugate of camptothecin and artesunate (C-Q) was prepared and its cytotoxicity was evaluated using the MTT assay. In addition, the antitumour activity and toxicity of C-Q were investigated in mice, and interaction between transferrin (TF) and C-Q was investigated to evaluate its interaction with biological macromolecules. In the MTT assay, C-Q showed better inhibitory activity against MCF7 breast cancer cells and SMMC-7721 liver cancer cells than camptothecin or artesunate. In vivo, C-Q showed lower toxicity and better antitumour activity compared with camptothecin. Fluorescence spectroscopy showed static quenching of TF in the presence of C-Q, and thermodynamic parameters (ΔH>0 and ΔG<0) indicated that the reaction was spontaneous and endothermic. The main binding force between C-Q and TF was hydrophobic, as indicated by thermodynamic parameters (ΔH>0 and ΔS>0). Thus, synchronous fluorescence spectra showed that C-Q had no influence on the conformation of TF. Our results indicated that C-Q represents a novel potential anticancer therapeutic vector with advantages over current methods of CPT and ART administration. This novel drug delivery system allows the use of these drugs in a manner associated with few side effects for normal tissue, and which facilitates synergistic effects of anti-tumour drugs.


Subject(s)
Antineoplastic Agents/chemistry , Artemisinins/chemistry , Camptothecin/chemistry , Drugs, Chinese Herbal/chemistry , Animals , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Artemisinins/isolation & purification , Artemisinins/pharmacology , Artesunate , Camptothecin/isolation & purification , Camptothecin/pharmacology , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Female , Liver/drug effects , Liver/metabolism , MCF-7 Cells , Mice , Mice, Inbred BALB C , Mice, Nude , Xenograft Model Antitumor Assays
13.
J Drug Target ; 22(6): 543-52, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24725118

ABSTRACT

Abstract Camptothecin-20(s)-O-glycine ester-[N-(3'α, 12'α-dihydroxy-24'-carbonyl-5'ß-cholan)] (A2), 10-(3'α,12'α-dihydroxy-5'ß-cholan-24'-carboxyl)-(20 s)-camptothecin (C2), and 10-O-(3-O-(3'α, 12'α-dihydroxy-24'-carbonyl-5'ß-cholan)-propyl)-(20S)-camptothecin (D2) are novel camptothecin-deoxycholic acid analogues. MTT assays were performed to assess the anticancer activity of these compounds against hepatocellular carcinoma SMMC-7721, breast carcinoma MCF-7, and colorectal carcinoma HCT-116 cells. A2 had a high killing ability on SMMC-7721 cells selectively, but C2 and D2 did not exhibit selectivity with regard to SMMC-7721 killing. Uptake assays were performed in an effort to elucidate the transport mechanisms of A2 into SMMC-7721 cells. A2 increased the mRNA expression of OATP1B3 (an organic anion-transporting polypeptide) and uptake of A2 was inhibited by rifampin (inhibitor of OATP1B3), which indicated that the transporter-mediated transport of A2 was mediated by OATP1B3. In addition, according to the western blot and apoptosis assays, we found that A2 killed SMMC-7721 cells by inducing cell apoptosis mainly via an AIF (apoptosis-inducing factor) pathway and a caspase-dependent mitochondria apoptosis pathway.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/pharmacology , Antineoplastic Agents, Phytogenic/pharmacokinetics , Apoptosis/drug effects , Base Sequence , Camptothecin/pharmacokinetics , Cell Line , DNA Primers , Humans , Organic Anion Transporters/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction
14.
Int J Pharm ; 465(1-2): 360-7, 2014 Apr 25.
Article in English | MEDLINE | ID: mdl-24530520

ABSTRACT

The purpose of this work is to prepare a formulation using mannitol coupling Camptothecin (CPT) nanoparticles (CPT-NPs) to circumvent the difficult solubilization practice based on central composite experimental statistical design. CPT-NPs were prepared with a high-pressure homogenization technique method. The independent variables considered for the optimization of CPT-NPs were percentage of CPT in raw material (CPT and mannitol), concentration of CPT in working liquid, cycles numbers and homogenizer pressure for drug loading efficiency, particle size and polydispersity index. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized CPT-NPs showed an appropriate drug loading efficiency (18.09 ± 2.13%), a homogeneous particle size (165.33 ± 37.23 nm) and a low polydispersity index (0.29 ± 0.01). The CPT-NPs group show higher inhibition ratio (79.95%) of H22 tumor growth in vivo compared with TPT and CPT at the same dose. Changes in mice body weight demonstrate CPT-NPs have the lower toxicity. The results of biodistribution studies indicated the obviously superiority of CPT-NPs in increasing the accumulation of CPT within tumor. Overall, CPT-NPs under optimum conditions are considered to be potentially feasible to overcome formulation challenges for drug delivery.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Camptothecin/pharmacology , Drug Carriers , Liver Neoplasms/drug therapy , Mannitol/chemistry , Nanoparticles , Analysis of Variance , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/metabolism , Camptothecin/administration & dosage , Camptothecin/chemistry , Camptothecin/metabolism , Cell Line, Tumor , Chemistry, Pharmaceutical , Female , Humans , Kinetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice , Models, Statistical , Particle Size , Solubility , Technology, Pharmaceutical/methods , Tissue Distribution , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
15.
Fitoterapia ; 90: 57-64, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23811430

ABSTRACT

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to identify and quantify the camptothecin quaternary derivative CPT8 for application in pharmacokinetics and tissue distribution studies. Rat plasma and tissue samples were extracted with methanol by using camptothecin as the internal standard (IS). Chromatographic separation of CPT8 and the IS was achieved using a Hypersil GOLD C18 column, with a flow rate of 1.0 mL/min followed by quantification with tandem mass spectrometry, operating with electrospray ionization in the positive ion mode and by applying multiple reaction monitoring. The MS/MS ion transitions were monitored at m/z 484.3-361.2 for CPT8 and m/z 349.0-305.2 for the IS (CPT). A calibration curve was constructed using CPT8 concentrations ranging from 2.5 ng/mL to 2500 ng/mL (r>0.993). The efficiency of CPT8 extraction from plasma and tissue samples ranged from 91.23% to 105.4%. Intra- and inter-day precision (relative standard deviation) values were 0.21% and 7.25%, respectively. No matrix effects were observed. The freeze-thaw stability, post-extraction stability, and stability following short- and long-term storage at low temperatures ranged from 84.12% to 108.2%. The preclinical data obtained using this method is expected to facilitate future clinical investigations of CPT8.


Subject(s)
Camptotheca/chemistry , Camptothecin/pharmacokinetics , Plant Extracts/pharmacokinetics , Animals , Camptothecin/analogs & derivatives , Chromatography, High Pressure Liquid/methods , Female , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry/methods , Tissue Distribution
16.
Article in English | MEDLINE | ID: mdl-22051412

ABSTRACT

In this study, the binding interactions of the water-soluble camptothecin derivatives hydroxycamptothecin (10-HCPT), topotecan (TPT), and camptothecin quaternary salt (CPT8), to bovine serum albumin (BSA) were determined using fluorescence spectra and UV-vis spectra. The results revealed that the fluorescence of BSA was strongly quenched by the binding of camptothecin derivatives to BSA. The quenching mechanism of the camptothecin derivatives was found to be static according to the Stern-Volmer equation. The binding constant and binding sites were confirmed by fluorescence quenching spectra. The thermodynamic parameters Gibbs free energy change (ΔG<0), enthalpy change (ΔH>0), and entropy change (ΔS>0) implied that the interaction process was spontaneous and endothermic, and the interaction forces between camptothecin compounds and BSA were found to be hydrophobic. According to Föster non-radioactive energy transfer, the binding distances between 10-HCPT, TPT, and CPT8, and BSA were determined to be 1.73nm, 1.63nm, and 1.61nm, respectively. The synchronous fluorescence spectra confirmed that the camptothecin compounds cannot cause conformational changes in BSA. A rapid and sensitive method for determining the binding interaction between water-soluble camptothecin derivatives and BSA was established based on these principles of fluorescence quenching.


Subject(s)
Camptothecin/metabolism , Serum Albumin, Bovine/metabolism , Water/chemistry , Animals , Binding Sites , Camptothecin/chemistry , Cattle , Energy Transfer , Kinetics , Protein Binding , Solubility , Spectrometry, Fluorescence , Temperature
17.
Molecules ; 16(9): 7803-14, 2011 Sep 13.
Article in English | MEDLINE | ID: mdl-22143544

ABSTRACT

Camptothecin-20(s)-O-[N-(3'α,12'α-dihydroxy-24'-carbonyl-5'ß-cholan)]-lysine (B2) is a novel camptothecin analogue. Our previous study had shown that it displayed higher cytoxicity activity towards hepatocellular carcinoma SMMC-7721 cells than camptothecin (CPT) in vitro. In this paper, the underlying mechanism of anti-proliferation of B2 towards SMMC-7721 cells was further examined. Cell growth inhibition of B2 was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; morphological changes were observed under Laser Scanning Confocal Microscope (LSCM); cell cycle distribution, apoptotic population, changes in mitochondrial membrane potential, intracellular calcium concentration and reactive oxygen species (ROS) production were determined by flow cytometry (FCM). Activities of caspase-3 and caspase-9 were measured, and the expression level of Bcl-2 and Bax proteins were analyzed by Western blot. The results suggested that B2 inhibited SMMC-7721 cell growth by causing cell cycle arrest at the S and G2/M phases, and induced apoptosis involving a mitochondrial pathway. B2 appears to cause a high induction of apoptosis on SMMC-7721 cells in vitro, which suggests it might be a potential drug for cancer therapy.


Subject(s)
Apoptosis/drug effects , Camptothecin/analogs & derivatives , Carcinoma, Hepatocellular/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Calcium/metabolism , Camptothecin/chemistry , Camptothecin/pharmacology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Line, Tumor/drug effects , Cell Proliferation/drug effects , Humans , Liver Neoplasms/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , bcl-2-Associated X Protein/metabolism
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